Development of Vaccines for High-Risk Ductal Carcinoma In situ of the Breast

With the widespread use of screening mammography, ductal carcinoma in situ (DCIS) has become the most frequently diagnosed cancerous lesion identified in the breast. Like invasive breast cancer, DCIS is heterogeneous and represents a relatively wide spectrum of diseases.

Low-grade DCIS either rarely develops into invasive disease or progresses slowly to invasiveness over the course of 8 to 10 years. On the other hand, if untreated, high-grade DCIS lesions that display comedonecrosis will likely develop into invasive breast cancers over a 5- to 7-year period. Following current conventional treatment with surgery with wide margins (lumpectomy; ref. 1), lumpectomy plus radiation therapy (2), or mastectomy, the overall prognosis for these patients is excellent. Nonetheless, many patients (at least 30%) require the more aggressive therapeutic option (mastectomy) either because of extensive disease or for fear of cancer recurrence.

The latter remains a significant risk, particularly in younger patients. Fortunately, the relatively long period of latency between the onset of DCIS and development of invasive breast cancer offers an opportunity for novel neoadjuvant interventions. The potential benefits of such neoadjuvant therapies include (a) reduction of risk for subsequent breast cancer, (b) reduction in the psychological effect of the disease related to fear of recurrence, and (c) reduction in the morbidity resulting from surgery and radiation.

The latter would be achieved through diminution in the extent of disease before the application of standard therapies, limiting the need for radiation and decreasing the need for extensive surgical